Phenotypes

Turner and Al-Chalabi 2007

Motor neurone disease comprises a number of clinical phenotypes united by the pathological feature of progressive motor neuronal loss. They can be distinguished on clinical and pathological fetaures.

The most common form of MND is amyotrophic lateral sclerosis, where there is clinical evidence of both upper and lower motor neurone involvement.

Clinically 'pure' lower motor neurone MND is termed progressive muscular atrophy, and pure upper motor neurone MND is termed primary lateral sclerosis. The latter is particularly rare and associated with significantly slower progression.

MND Australia 2011 - More Facts

The disease can be classified into four main types depending on the pattern of motor neurone involvement and the part of the body where the symptoms begin.
1. Global Type

• both upper and lower motor neurones are affected - includes amyotrophic lateral sclerosis (ALS) and progressive bulbar palsy (PBP)
•  ALS is the most common form, characterised by muscle weakness and stiffness, over-active reflexes and, in some cases, rapidly changing emotional expression. Initially the limbs cease to work properly. The muscles of speech, swallowing and breathing are usually also later affected
• PBP, mixed bulbar palsy and pseudobulbar palsy are forms that involve the muscles of speech and swallowing. The nerves that control these functions are located in the bulb (the lower part of the brain), hence the term bulbar palsy (paralysis). The limb muscles may also later be affected

2. Flail Arm Type and
3. Flail Leg Type

• lower motor neurones are affected - slower rates of progression and significantly longer survival compared to ALS and PBP characterised by absent reflexes, muscle wasting and weakness. Flail Arm begins in the arms. Flail Leg begins in the legs

4. Primary Lateral Sclerosis Type

• upper motor neurones are affected - very rare form of the disease and the diagnosis is often provisional until at least two years have passed without LMN signs.

Progressive muscular atrophy (PMA)

A form of MND characterised initially by lower motor neurone signs resulting in more generalised muscle wasting and weakness, loss of weight and muscle twitching. PMA can be the hardest form of MND to diagnose accurately

recent studies indicate that many people diagnosed with PMA subsequently develop upper motor neurone signs. This would lead to a reclassification to ALS.

MND Australia 2009

Medical literature.. ..generally uses the term amyotrophic lateral sclerosis (ALS) as an umbrella term to include progressive bulbar palsy (PBP). This is because there is:

• uncertainty about the cause and mechanism of motor neurone deterioration
• debate about the extent to which different forms are simply variations in the same disease process or whether there are several different disease mechanisms
• international difference in terms used to describe motor neurone disease.
  

Talman and others 2009

(Observed patterns of MND/ALS patients) ...a method for assisting allocation of patients with similar clinical appearance was developed which recognized the observed patterns of disease presentation and progression. The region of symptom onset and the distribution of lower motor neuron (LMN), combined upper and lower motor neuron (UMN/LMN) or upper motor neuron (UMN) signs were determined for each region, bulbar, cervical and lumbar.

The four distinct clinical phenotypes: Global, Flail Arm, Flail Leg and Primary Lateral Sclerosis (PLS) demonstrated significantly different rates of progression and survival times.